INDIVIDUAL LOCOMOTOR RESPONSE TO NOVELTY PREDICTS SELECTIVE ALTERATIONS IN D-1 AND D-2 RECEPTORS AND MESSENGER-RNAS

Rats that have a greater locomotor response to novelty (high responder s, HR) have differences in measures of presynaptic dopamine transmissi on compared to low responders (LR) to a novel environment, including a ltered dopamine release and behavioral response to indirect dopamine a gonists. This study examined the role of three dopamine terminal field s, the nucleus accumbens, striatum, and medial prefrontal cortex, in d ifferences between HR and LR. In the first experiment, dopamine was in fused directly into the nucleus accumbens (0, 3, 10, and 30 mu g/side) or the striatum (0, 10, 30, and 100 mu g/side). HR showed a greater b ehavioral response to both the 3 and 30 mu g/side doses infused into t he nucleus accumbens compared to LR. No differences between HR and LR were revealed by dopamine infusion into the striatum. In the second ex periment, radioligand binding assays were performed to determine if di fferences exist between high and low responder rats in the B-max and/o r K-D of radiolabeled antagonist ligands for the dopamine D-1 and/or D -2 receptors. There were fewer D-2 binding sites in the nucleus accumb ens and fewer sites in the striatum in HR compared to LR. High respond ers showed a greater B-max for D-1 binding sites in the nucleus accumb ens than LR. No differences in number of binding sites for D-2 recepto rs were observed between HR and LR in the striatum. No differences bet ween HR and LR in D-2 or D-1 receptor binding were observed in the med ial prefrontal cortex. There were no differences in K-D for any of the dopamine receptors in the regions examined. In experiment three, mRNA content for D-1 and D-2 receptors was evaluated in the nucleus accumb ens, striatum, and the medial prefrontal cortex. HR showed a reduction in mRNA content for D-2 receptors compared to LR in the nucleus accum bens. No significant differences between HR and LR in D-2 mRNA content were observed in the striatum or medial frontal cortex. In addition, no differences between HR and LR were observed in D-1 mRNA content in the three regions examined. The final experiment evaluated the dopamin e transporter. The B-max of binding to the dopamine transporter in the nucleus accumbens, striatum, or prefrontal cortex was not different b etween HR and LR. Likewise, the content for dopamine transporter mRNA in the substantia nigra did not differ. However, in the nucleus accumb ens, but not the striatum, the velocity of dopamine uptake was greater in HR than in LR. It is concluded that alterations in postsynaptic do pamine transmission in the nucleus accumbens may partly mediate the lo comotor response of an animal to a novel environment. The nucleus accu mbens is of greater importance in differences between HR and LR than e ither the striatum or medial frontal cortex, and decreases in D-2 rece ptor density and mRNA are more marked than changes in D-1 receptors.